Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
Department of Medicine, The Graduate School, Yonsei University, Seoul, Korea.
Helicobacter. 2019 Feb;24(1):e12547. doi: 10.1111/hel.12547. Epub 2018 Nov 15.
Despite recent advances in studies on the gastric microbiome, the role of the non-Helicobacter pylori gastric microbiome in gastric carcinogenesis remains unclear. We evaluated the characteristics of the gastric microbiome and metagenomic functions in patients with IM.
Participants were classified into six groups according to disease status (chronic superficial gastritis [CSG], intestinal metaplasia [IM], and cancer) and H. pylori- infection status (H. pylori-positive and H. pylori-negative). The gastric microbiome was analyzed in mucosal tissues at the gastric antrum by 16S rRNA gene sequencing. Moreover, we assessed the metagenome including the type IV secretion system (T4SS) gene, as T4SS proteins are essential for transferring CagA from H. pylori- into the human gastric epithelium.
Among the 138 included patients, 48, 9, 23, 14, 12, and 32 were classified into the H. pylori-negative CSG, H. pylori-negative IM, H. pylori-negative cancer, H. pylori-positive CSG, H. pylori-positive IM, and H. pylori-positive cancer groups, respectively. Cyanobacteria were predominant in the H. pylori-negative CSG group compared to in the H. pylori-negative IM and H. pylori-negative cancer groups (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 14.0% vs 4.2% vs 0.04%, P < 0.001). In contrast, Rhizobiales were commonly observed in the H. pylori-negative IM group (H. pylori-negative CSG vs H. pylori-negative IM vs H. pylori-negative cancer: 1.9% vs 15.4% vs 2.8%, P < 0.001). The relative abundance of Rhizobiales increased as H. pylori-infected stomachs progressed from gastritis to IM. In the H. pylori-negative IM group, genes encoding T4SS were prevalent among the metagenome. Additionally, after H. pylori- eradication therapy, the gastric microbiome was similar to the microbiome observed after spontaneous clearance of H. pylori-.
The relative abundance of Rhizobiales was higher in patients with H. pylori-negative IM than in those with H. pylori-negative CSG or cancer. Additionally, T4SS genes were highly observed in the metagenome of patients with IM. Highly abundant T4SS proteins in these patients may promote gastric carcinogenesis.
尽管近年来在胃微生物组研究方面取得了进展，但非幽门螺杆菌胃微生物组在胃癌发生中的作用仍不清楚。我们评估了 IM 患者胃微生物组的特征和宏基因组功能。
根据疾病状态（慢性浅表性胃炎[CSG]、肠上皮化生[IM]和癌症）和幽门螺杆菌感染状态（幽门螺杆菌阳性和幽门螺杆菌阴性），将参与者分为六组。通过 16S rRNA 基因测序分析胃窦黏膜组织中的胃微生物组。此外，我们评估了宏基因组，包括 IV 型分泌系统（T4SS）基因，因为 T4SS 蛋白对于将 CagA 从幽门螺杆菌转移到人类胃上皮细胞至关重要。
在纳入的 138 名患者中，48 名、9 名、23 名、14 名、12 名和 32 名分别被归类为幽门螺杆菌阴性 CSG、幽门螺杆菌阴性 IM、幽门螺杆菌阴性癌症、幽门螺杆菌阳性 CSG、幽门螺杆菌阳性 IM 和幽门螺杆菌阳性癌症组。与幽门螺杆菌阴性 IM 组和幽门螺杆菌阴性癌症组相比，幽门螺杆菌阴性 CSG 组中蓝细菌更为普遍（幽门螺杆菌阴性 CSG 与幽门螺杆菌阴性 IM 与幽门螺杆菌阴性癌症：14.0% 与 4.2% 与 0.04%，P<0.001）。相反，根瘤菌在幽门螺杆菌阴性 IM 组中很常见（幽门螺杆菌阴性 CSG 与幽门螺杆菌阴性 IM 与幽门螺杆菌阴性癌症：1.9% 与 15.4% 与 2.8%，P<0.001）。随着受幽门螺杆菌感染的胃从胃炎发展到 IM，Rhizobiales 的相对丰度增加。在幽门螺杆菌阴性 IM 组中，宏基因组中存在编码 T4SS 的基因。此外，在幽门螺杆菌根除治疗后，胃微生物组与自发清除幽门螺杆菌后的微生物组相似。
与幽门螺杆菌阴性 CSG 或癌症患者相比，幽门螺杆菌阴性 IM 患者 Rhizobiales 的相对丰度更高。此外，IM 患者的宏基因组中高度观察到 T4SS 基因。这些患者中丰富的 T4SS 蛋白可能促进胃癌的发生。
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